Glycation is a non-enzymatic process involving a saccharide (glucose or ribose) which reacts via the Maillard reaction with an amine group of an amino acid residue (for instance lysine), particularly an amino acid residue of a protein, to form a Schiffs base. This base, after an Amadori molecular rearrangement, may lead, via a succession of reactions, to bridging, particularly intramolecular bridging, for instance of pentosidine type.
This phenomenon increases regularly with age. It is characterized by the appearance of glycation products, the content of which increases uniformly as a function of age. Glycation products are, for example, pyrraline, carboxymethyllysine, pentosidine, crossline, Nε(2-carboxyethyl)lysine (CEL), glyoxal-lysine dimer (GOLD), methylglyoxal-lysine dimer (MOLD), 3DG-ARG imidazolone, versperlysines A, B, C, threosidine, or advanced glycosylation end products or AGEs.
The glycation of proteins is thus a universal phenomenon, which is well known as regards the skin, particularly as regards its dermal component, but which also takes place in the skin appendages such as the nails or the hair, particularly on keratins and more generally throughout the protein system, provided that the conditions required for glycation are met.
Human skin is constituted of two compartments, namely an upper compartment, the epidermis, and a deep compartment, the dermis.
Natural human epidermis is composed mainly of three types of cells, namely keratinocytes, which form the vast majority, melanocytes and Langerhans cells. Each of these cell types contributes by virtue of its intrinsic functions to the essential role played in the body by the skin.
The dermis provides the epidermis with a solid support. It is also its nourishing element. It is mainly formed from fibroblasts and an extracellular matrix which is itself composed of various extracellular proteins, among which are especially collagen fibres, elastin and various glycoproteins. All of these extracellular components are synthesized by the fibroblasts. Leukocytes, mastocytes or tissue macrophages are also found in the dermis. Finally, the dermis contains blood vessels and nerve fibres.
Fibroblasts, via their activity in the synthesis of extracellular matrix proteins (proteoglycans, collagen fibres and other structural glycoproteins) are the main actors in the structural development of the dermis.
Collagen fibres give the dermis its solidity. They are very strong, but sensitive to certain enzymes generally known as collagenases. In the dermis, collagen fibres are formed from fibrils sealed together, thus forming more than 10 different types of structures. The structure of the dermis is in large part due to the entanglement of the collagen fibres packed together. The collagen fibres contribute to the tonicity of the skin.
The collagen fibres are regularly renewed, but this renewal decreases with age, which leads especially to thinning of the dermis. It is also accepted that extrinsic factors such as smoking or certain treatments (retinoic acid and derivatives, glucocorticoids, vitamin D and derivatives, for example) also have an effect on the skin and on its collagen content.
As regards the dermal component of the skin, glycation takes place mainly in the dermis, on collagen fibres, according to the process described above. The glycation of collagen increases uniformly with age, leading to a uniform increase in the content of glycation products in the skin.
Without wishing to introduce any theory of ageing of the skin, it should be noted that other changes in collagen might also be a consequence of glycation, such as a decrease in heat denaturation, an increase in resistance to enzymatic congestion and an increase in intermolecular bridging. These effects were able to be demonstrated in the course of ageing of the skin (Tanaka S. et al., 1988, J. Mol. Biol., 203, 495-505; Takahashi M. et al., 1995, Analytical Biochemistry, 232, 158-162). Furthermore, glycation-mediated changes in certain constituents of the basal membrane such as collagen IV, laminin and fibronectin were able to be demonstrated (Tarsio J F. et al., 1985, Diabetes, 34, 477-484; Tarsio J. F. et al., 1988, Diabetes, 37, 532-539; Sternberg M. et al., 1995, C. R. Soc. Biol., 189, 967-985).
It is thus understood that, in the course of ageing of the skin, the physicochemical properties of collagen become modified and collagen becomes more difficult to dissolve and more difficult to degrade.
Thus, one of the components of aged skin clearly appears to be glycated collagen.
It is known that the skin results from a close association between at least two compartments from which it is constituted, namely the epidermis and the dermis. The interactions between the dermis and the epidermis are such that it is reasonable to think that a change in one may have consequences on the other. It may be suspected that ageing of the dermis in particular with its glycation phenomena is bound to have consequences on the epidermis associated therewith. Thus, in the course of ageing of the skin, the glycation of collagen must lead to changes in the epidermis that necessarily contribute towards the ageing of the epidermis.
Thus, if the glycation of dermal proteins, particularly collagen, has so many detrimental consequences in the skin, similar consequences are to be expected of the glycation of proteins in the skin appendages, for instance the nails and/or the hair and, for that matter, of any protein system.
The need for products that reduce the phenomenon of protein glycation may thus be understood.